Abstract 1413: Activation of Wnt11 Signaling Enhances MSC-Mediated Ischemic Heart Repair via Promoting Their Transdifferentiation in Infarcted Myocardium
We hypothesize that Wnt11 transfected mesenchymal stem cells (MSCsWnt11) have a higher potential for regenerating infarcted myocardium. MSCs were transfected with Wnt11 using Clontech pMSCV retroviral expression system and MSCs transfected with GFP was served as a control. Microarray and quantitative PCR were used to assay the expression of various genes. MSCs (1.5×106/50μl) were transplanted into the border area of rat infarcted myocardium induced by ligation of the left anterior descending coronary artery (LAD). MSCs were also co-cultured with neonatal rat cardiomyocyte (CM). Cardiac function was significantly improved in the hearts transplanted with MSCsWnt11 compared to MSCsGFP as measured by echocardiography after LAD ligation (Fig. A⇓). A marked reduction in left ventricle fibrosis (Fig. B⇓) and TUNEL positive cell was observed in MSCsWnt11 group. Gene analysis indicated that the expression of Wnt11 was 204~243 fold higher in MSCsWnt11 than that in MSCsGFP. Wnt11 upregulated the expression of various myogenic genes, e.g. GATA-4, BNP and Islet-1 in MSCs (Fig. C⇓). After co-culture with CM for 7 days, the differentiation rate in MSCWnt11 (27.4%) was significantly higher than that in MSCsGFP (17.8%). Co-culturing with MSCsWnt11 apparently reduced hypoxia-induced CM injury as shown by nucleosome ladder upon agarose gel electrophoresis, annexin-V positive cells (Fig. D⇓) and reduced LDH release from CM (Fig. E⇓). Wnt11 signaling enhances MSC-mediated ischemic heart repair by promoting transdifferentiation of MSCs into cardiomyocytes and attenuating apoptosis.